Ketanserin reduces a particular monoamine pool in peripheral tissues.

The effect of ketanserin and tetrabenazine treatment on monoamine and metabolite levels in central and peripheral tissues was investigated in young and senescent male Wistar and spontaneously hypertensive Okamota rats. Control animals showed significantly higher brain monoamine levels and 3 and 5.5 times higher dopamine levels in the vas deferens of the senescent and hypertensive rats, as compared with young normotensive rats. Ketanserin (20 mg/kg) produced an average of 20% reduction of brain monoamines without changing metabolite levels. In the vas deferens, dopamine was reduced by 85% and norepinephrine by 30%. In cardiovascular tissues, norepinephrine was 40% to 50% decreased and in the spleen norepinephrine was 60% and 5-hydroxytryptamine 30% reduced. Ketanserin (5 mg/kg) had only a marked effect on dopamine in the vas deferens and on norepinephrine in the portal vein. Tetrabenazine at 20 mg/kg produced complete depletion of the monoamine and 3-methoxytyramine levels in the brain with a concomitant rise in acid metabolites. In peripheral tissues, amine levels were reduced by 55% to 80%; dopamine in the vas deferens was 93% decreased. Tetrabenazine (5 mg/kg) still had marked effects in all tissues. The drug effects were the same in the three types of rats and the effects did not markedly change with chronic treatment up to 20 days. It is hypothesized that at least two different mechanisms are involved in monoamine depletion, 1) the classically proposed inhibition of uptake of monoamines in the storage vesicles, a property of tetrabenazine not shared by ketanserin in vivo and 2) triggering of the release of monoamines from a ketanserin-sensitive pool, which is relatively more important in peripheral tissues than in the brain. The latter process is probably mediated by previously identified ketanserin-binding release sites on nerve terminals and platelets. The ketanserin-sensitive monoamine pools in peripheral tissues may have a role in cardiovascular pathologies.